Prospective Inception Cohort Study Research Articles

The Effect of Social Isolation on 1-Year Outcomes After Surgical Repair of Low-Energy Hip Fracture.

To evaluate whether social isolation or loneliness is associated with outcomes 1 year after low-energy hip fracture. Prospective inception cohort study. Academic level I trauma center. Participants were 65 years or older and enrolled 2-4 days after surgery for a first low-energy hip fracture. Exclusion criteria were bilateral or periprosthetic hip fracture, previous hip fracture, non-English speaking, international address, active cancer, stage 4 cancer in the past 5 years, radiation to the hip region, and cognitive impairment. Participants were followed longitudinally for 1 year. The patient-reported outcomes measurement information system (PROMIS)-29 was elicited 2-4 days postoperatively and 1 year later. Patient-reported risk factors included the Lubben Social Networks Scale and the University of California, Los Angeles Loneliness Scale, which were compared with the lower extremity activity scale and PROMIS-29 domains. Three hundred and twenty-five patients were enrolled. Participants had a median age of 81.7 years, were 70.9% female, and were 85.9% White. In total, 31.6% of patients were socially isolated at the time of fracture. At 1 year, 222 of the 291 subjects who were confirmed alive at 1 year provided data. Multivariable linear models were performed separately for each outcome, including lower extremity activity scale and PROMIS-29 domains. Controlling for age, sex, education, and body mass index, those who were socially isolated at the time of fracture had worse PROMIS-29 function (β = -3.83; P = 0.02) and ability to participate in social roles (β = -4.17; P = 0.01) at 1 year. Secondary analyses found that prefracture loneliness was associated with clinically meaningfully worse function, anxiety, depression, fatigue, sleep, pain, and ability to participate in social roles at 1 year (all P < 0.01). Prefracture social isolation was associated with worse outcomes 1 year after surgical repair of low-energy hip fracture. These data suggest loneliness may be more strongly associated with important patient-centric metrics than prefracture social isolation. Given the dearth of modifiable risk factors in this population, future studies are needed to evaluate whether improving social connections could affect outcomes in this rapidly growing demographic. Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

P1172 Epidemiology and initial presentation of newly diagnosed inflammatory bowel diseases in a Danish population-based inception cohort – results from the IBD Prognosis Study

Abstract Background It is unclear whether the incidence of inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), continues to increase. In this study, we aimed to investigate the occurrence and initial disease presentation of IBD in a population-based setting. In addition, we aimed to identify predictors of an early severe disease presentation. Methods The study was conducted as part of IBD Prognosis Study, an ongoing Danish prospective population-based inception cohort study that includes incident patients with IBD according to the Copenhagen Diagnostic Criteria since May 2021, covering the catchment areas of approximately 20% of the Danish population (1.1 million). In this analysis, cutoff for data analysis was in May 2023. Crude incidence rates and European Standard Population (ESP)-adjusted rates were calculated. A multivariable logistical regression model was constructed to identify predictors of a severe disease presentation, defined as the composite need for systemic steroids, immunomodulators, biologics, or IBD-related surgery within three months of disease. Results In total, 554 patients (UC: 344, CD: 210) fulfilled the inclusion criteria, resulting in the following crude incidence rates per 100,000 person-years: IBD 23.4 (95% CI 21.5-25.4), UC 14.0 (12.6-15.6), and CD 8.6 (7.4-9.8). ESP-adjusted rates were: IBD 20.4 (18.2-22.9), UC 11.8 (10.2-13.0), and CD 7.9 (6.5-9.9) (Figure 1). Among patients with UC, 81 (26.3%) and 95 (30.8%) had left-sided or extensive colitis at disease onset, respectively, while 61 (30.3%) and 62 (30.8%) patients with CD had ileal or ileocolonic disease. Stricturing or penetrating CD behaviour was observed in 24 (11.9%) and 11 (5.5%) patients, respectively. A high proportion of patients needed hospitalization (CD: 68 (33.8%), UC: 60 (19.5%), p=0.001) and IBD-related surgery (CD: 21 (10.4%), UC: 10 (3.2%), p=0.004) at the time of diagnosis. In multivariable analysis, a severe disease presentation of UC at the time of diagnosis was associated with left-sided or extensive disease distribution, thrombocytosis, and increased levels of C-reactive protein (CRP) (Table 1). In patients with CD, stricturing, or perianal disease, as well as anemia, levels of albumin, CRP, and calprotectin were predictive of this endpoint (Table 1). Conclusion The incidence of UC and CD in Denmark appears stable compared to historical data from the previous decades.1 The study identified clinical predictors of a severe disease presentation from the time of diagnosis, emphasizing the critical need for early risk stratification and intervention strategies. Reference: 1 Dorn-Rasmussen M et al., J Crohns Colitis. doi: 10.1093/ecco-jcc/jjac138.

The clinical course of acute, subacute and persistent low back pain: a systematic review and meta-analysis.

Understanding the clinical course of low back pain is essential to informing treatment recommendations and patient stratification. Our aim was to update our previous systematic review and meta-analysis to gain a better understanding of the clinical course of acute, subacute and persistent low back pain. To update our 2012 systematic review and meta-analysis, we searched the Embase, MEDLINE and CINAHL databases from 2011 until January 2023, using our previous search strategy. We included prospective inception cohort studies if they reported on participants with acute (< 6 wk), subacute (6 to less than 12 wk) or persistent (12 to less than 52 wk) nonspecific low back pain at study entry. Primary outcome measures included pain and disability (0-100 scale). We assessed risk of bias of included studies using a modified tool and assessed the level of confidence in pooled estimates using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. We used a mixed model design to calculate pooled estimates (mean, 95% confidence interval [CI]) of pain and disability at 0, 6, 12, 26 and 52 weeks. We treated time in 2 ways: time since study entry (inception time uncorrected) and time since pain onset (inception time corrected). We transformed the latter by adding the mean inception time to the time of study entry. We included 95 studies, with 60 separate cohorts in the systematic review (n = 17 974) and 47 cohorts (n = 9224) in the meta-analysis. Risk of bias of included studies was variable, with poor study attrition and follow-up, and most studies did not select participants as consecutive cases. For the acute pain cohort, the estimated mean pain score with inception time uncorrected was 56 (95% CI 49-62) at baseline, 26 (95% CI 21-31) at 6 weeks, 22 (95% CI 18-26) at 26 weeks and 21 (95% CI 17-25) at 52 weeks (moderate-certainty evidence). For the subacute pain cohort, the mean pain score was 63 (95% CI 55-71) at baseline, 29 (95% CI 22-37) at 6 weeks, 29 (95% CI 22-36) at 26 weeks and 31 (95% 23-39) at 52 weeks (moderate-certainty evidence). For the persistent pain cohort, the mean pain score was 56 (95% CI 37-74) at baseline, 48 (95% CI 32-64) at 6 weeks, 43 (95% CI 29-57) at 26 weeks and 40 (95% CI 27-54) at 52 weeks (very low-certainty evidence). The clinical course of disability was slightly more favourable than the clinical course of pain. Participants with acute and subacute low back pain had substantial improvements in levels of pain and disability within the first 6 weeks ( moderate-certainty evidence); however, participants with persistent low back pain had high levels of pain and disability with minimal improvements over time (very low-certainty evidence). Identifying and escalating care in individuals with subacute low back pain who are recovering slowly could be a focus of intervention to reduce the likelihood of transition into persistent low back pain. PROSPERO - CRD42020207442.

Improved clinical outcomes with early anti-tumour necrosis factor alpha therapy in children with newly diagnosed Crohn's disease: real world data from the international prospective PIBD-SETQuality inception cohort study.

Treatment guidelines for paediatric Crohn's disease (CD) suggest early use of anti-tumour necrosis factor alpha (anti-TNF) in high-risk individuals. The aim is to evaluate the effect of early anti-TNF in a real-world cohort. Children with newly-diagnosed CD were prospectively recruited at 28 participating sites of the international observational PIBD-SETQuality study. Outcomes were compared at 3 months, 1 and 2 years between patients receiving early anti-TNF (<90 days after diagnosis) and those not receiving early anti-TNF. Outcomes included sustained steroid-free remission (SSFR) without treatment intensification (specified as SSFR*) and sustained steroid-free mild/inactive disease without treatment intensification (specified as SSFMI*). Penalised logistic regression model-based standardisation was applied to estimate the relative risks (RR) of early therapy on outcomes. RRs were estimated for high-risk and low-risk patients based on presence of predictors of poor outcome (POPOs) and disease activity at diagnosis. In total, 331 children (median age 13.9 years [IQR 12.2 - 15.3]) were enrolled, with 135 (41%) receiving early anti-TNF. At 1 year, patients on early anti-TNF had higher rates of SSFR* (30% vs. 14%, p<0.001) and SSFMI* (69% vs. 33%, p<0.001), with RRs of 2.95 (95%CI 1.63-5.36) and 4.67 (95%CI 2.46-8.87) respectively. At 1 year, the RRs for SSFMI* were higher, and statistically significant in high-risk patients, i.e. those with moderate/severe disease compared to mild/inactive disease at diagnosis (5.50 [95%CI 2.51-12.05]) vs. 2.91 [95%CI 0.92-9.11]), and those with any POPO compared to no POPO (5.05 [95%CI 2.45-10.43] vs. 3.41 [95%CI 0.54-21.7]). In this cohort of children with newly-diagnosed CD, early anti-TNF demonstrated superior effectiveness in high-risk patients.

Demographic and clinical profile of an inception cohort of road trauma survivors

BackgroundRoad trauma is a major public health concern, often resulting in reduced health-related quality of life and prolonged absenteeism from work even after so-called ‘minor’ injuries that do not result in hospitalization. This manuscript compares pre-injury health, sociodemographic characteristics and injury details between age, sex, and road user categories in a cohort of 1,480 road trauma survivors.MethodsThis was a prospective observational inception cohort study of road trauma survivors recruited between July 2018 and March 2020 from three trauma centres in British Columbia, Canada. Participants were aged ≥ 16 years and arrived in a participating emergency department within 24 h of involvement in a motor vehicle collision. Data were collected from structured interviews and review of medical records.ResultsThe cohort of 1,480 road trauma survivors included 280 pedestrians, 174 cyclists, 118 motorcyclists, 683 motor vehicle drivers, and 225 passengers. Median age was 40 (IQR = [27, 57]) years; 680 (46%) were female. Males and younger patients were significantly more likely to report better pre-injury physical health. Motorcyclists and cyclists tended to report better physical health and less severe somatic symptoms, whereas pedestrians and motor vehicle drivers reported better mental health. Injury severity and hospital admission rates were higher in pedestrians and motorcyclists and lower in motorists. Upper and lower extremity injuries were most common in pedestrians, cyclists and motorcyclists, whereas neck injuries were most common in motor vehicle drivers and passengers.ConclusionsIn a large cohort of road trauma survivors, overall injury severity was low. Motorcyclists and pedestrians, but not cyclists, had more severe injuries than motorists. Extremity injuries were more common in vulnerable road users. Future research will investigate one-year recovery outcomes and identify risk factors for poor recovery.

Role of depressive symptoms on the development of pelvic girdle pain in pregnancy: A prospective inception cohort study.

Pelvic girdle pain in pregnancy is a major public health concern. For too many women, the pain condition causes disability and sick leave, has a negative impact on daily life, and breeds doubt in their view as mother, partner, and worker. The pathophysiology is unknown and causal treatment is lacking. Depression in pregnancy is common, undertreated, and previously associated with pelvic girdle pain with unclear causal direction. A prospective inception cohort study of 356 Swedish women examined them in early and late pregnancy. Women with a positive Posterior Pelvic Pain Provocation test in early pregnancy were not included. The exposure, depressive symptoms in early pregnancy, was self-reported on the Hospital Anxiety and Depression Scale, depression part (0-21). Outcome measure in late pregnancy was a graded score on the Posterior Pelvic Pain Provocation test (0-8). Covariates for statistical adjustment were identified in a directed acyclic graph. Linear robust and logistic regression were used in the statistical analyses. In early pregnancy, the 248 women with negative Posterior Pelvic Pain Provocation test had a mean score of 2.35 (± 2.3 standard deviation) on the Hospital Anxiety and Depression Scale, depression part. In a fully adjusted, multiple robust regression model a positive association was shown between Hospital Anxiety and Depression Scale score, depression part, and the Posterior Pelvic Pain Provocation test score in late pregnancy with an estimated effect of β=0.32 (95% confidence interval [CI] 0.16-0.48, p < 0.001). Dichotomization of exposure (Hospital Anxiety and Depression Scale, depression part <8/≥8) and outcome (Posterior Pelvic Pain Provocation test score 0/>0) rendered adjusted odds ratio 1.71 (95% CI 0.38-7.7) and numbers needed to treat adjusted odds ratio 5.54 (95% CI -3.4-14.5). Depressive symptoms in early pregnancy were associated with the development and intensity of pelvic girdle pain in late pregnancy. Considering the small sample size, screening and treatment for depressive symptoms in early pregnancy may enable a way to reduce and prevent disabling pelvic girdle pain in late pregnancy. Trials are needed to confirm the results.

Recurrence of low back pain: A difficult outcome to predict. Development and validation of a multivariable prediction model for recurrence in patients recently recovered from an episode of non-specific low back pain

BackgroundRecurrence of low back pain (LBP) is common. If clinicians could identify an individual's risk of recurrence, this would enhance clinical decision-making and tailored patient care. Objective/designTo develop and validate a simple tool to predict the probability of a recurrence of LBP by 3- or 12-months following recovery. MethodsData utilised for the prediction model development came from a prospective inception cohort study of participants (n = 250) recently recovered from LBP, who had sought care from chiropractic or physiotherapy services. The outcome measure was a recurrence of activity-limiting LBP. Candidate predictor variables (e.g., basic demographics, LBP history, levels of physical activity, etc) collected at baseline were considered for inclusion in a multivariable Cox model. The model's performance was tested in a separate validation dataset of participants (n = 261) involved in a randomised controlled trial investigating exercise for the prevention of LBP recurrences. ResultsThe final model included the number of previous episodes, total sitting time, and level of education. In the development sample, discrimination was acceptable (Harrell's C-statistic = 0.61, 95% CI, 0.59–0.62), but in the validation sample, discrimination was poor (0.56, 95% CI, 0.54–0.58). Calibration of the model in the validation dataset was acceptable at 3 months but was less precise at 12 months. ConclusionThe developed prediction model, which included number of previous episodes, total sitting time, and level of education, did not perform adequately in the validation sample to recommend its use in clinical practice. Predicting recurrence of LBP in clinical practice remains challenging.

Smoking, but not use of complementary and alternative medicine predicts residual functional disability in patients with inflammatory arthritis on biologic disease‐modifying anti‐rheumatic drugs: Results from the Singapore National Biologics Register

To describe inflammatory arthritis (IA) patients initiating biologic disease-modifying anti-rheumatic drugs (bDMARDs) who use complementary and alternative medicine (CAM), and determine the impact of CAM on predicting modified Health Assessment Questionnaire (mHAQ) at 6months. This was a prospective inception cohort study of patients ≥21 years old initiating a bDMARD for IA after July 2016. Data were obtained via questionnaires and abstraction from medical records. Baseline characteristics between ever-CAM and CAM non-users were compared. CAM as a predictor of mHAQ ≥1 at 6months after bDMARD initiation was analyzed using multivariate logistic regression, adjusting for other baseline characteristics. We recruited 299 patients (36.2% male, mean age 49.0 years). There were 45.8% who had rheumatoid arthritis, 54.2% had a spondyloarthropathy, median disease duration of 1.1 years and median mHAQ of 0.4. Compared to CAM non-users, ever-CAM users had a lower mean body mass index, were less likely to speak English, and more likely to smoke and drink alcohol. There was no association of CAM use with high mHAQ and no interaction with smoking. Smoking (odds ratio [OR] 938.9; 95% CI 3.20-275 884.1), baseline mHAQ (OR 252.2; 95% CI 5.34-11 899.2) and Charlson's Comorbidity Index score ≥4 (OR 237.4; 95% CI 1.22-46 184.4) independently predicted high mHAQ at 6months. CAM use was not associated with high mHAQ at 6months. Smoking was an independent predictor of residual functional disability at 6months, even after adjusting for age, comorbidity and baseline mHAQ. Greater emphasis on smoking cessation may improve long-term functional outcomes in IA patients on bDMARDs.

P158 Intestinal Ultrasound at IBD diagnosis predicts surgery – a Copenhagen IBD cohort study

Abstract Background The disease course of inflammatory bowel disease (IBD) is heterogeneous and unpredictable. Currently, we are unable to predict which patients will need IBD-related bowel resection in the first year after diagnosis. Intestinal Ultrasound (IUS) has been proven as a non-invasive modality for assessing disease activity in IBD. However, the evidence for IUS as a predictor of disease course is still limited. Here we present novel data on the predictive value of IUS performed at the time of IBD diagnosis. Methods Patients with new-onset IBD are currently being included in the ongoing multicentre prospective inception cohort study, the IBD Prognosis Study (May 2021 – April 2023). IUS is performed at the time of diagnosis and the patients are followed prospectively. Patients with proctitis are not assessed with IUS. The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) is calculated for the most inflamed segment with a high score indicating severe disease activity. IBUS-SAS (0-100) incorporates the bowel wall thickness (BWT), bowel wall stratification, colour Doppler signal, and inflammatory fat. Surgery was defined as an IBD-related bowel resection. Patients treated with corticosteroids for &amp;gt; 72 hours or with any IBD-treatment &amp;gt; two weeks prior to IUS were excluded from analysis. In this abstract, we report our preliminary results after including patients for 16 months. Results IBUS-SAS at diagnosis was available in 133 patients (out of 242 included). 68 patients were diagnosed with Crohn’s disease (CD) (ilieal: 22, colonic: 23, ileocolonic: 23) and 65 patients were diagnosed with ulcerative colitis (UC) or unclassified IBD (left-sided colitis: 20, extensive colitis: 45). Median follow-up was 226 days. During follow-up 10 patients underwent surgery (7.5%). These included 4 patients with UC (extensive colitis: 3, left-sided colitis: 1) and 6 patients with CD (ileal: 2, colonic: 2, ileocolonic: 2). Mean IBUS-SAS at diagnosis was 92.6 among patients who underwent surgery during follow-up vs. 48.8 for patients who did not undergo surgery (p&amp;lt;0.0001). Distribution of scores is shown in Figure 1. Mean BWT at diagnosis was 8.3 mm among patients who underwent surgery during follow-up vs. 5.0 mm for patients who did not undergo surgery (p&amp;lt;0.0001). In total, 12 patients had an IBUS-SAS &amp;gt; 90 at diagnosis and among these 7 (58.3%) were operated during follow-up. Figure 2 shows a Kaplan-Meier Curve of surgical free survival stratified by IBUS-SAS at diagnosis. Conclusion IUS activity at diagnosis of IBD seems to have the capability to predict short term risk of IBD-related surgery. Our results suggest IUS might be used at diagnosis to identify patients at high risk of IBD-related surgery.

Recent Advance Analysis of Recovery in Hospitalized People with COVID-19: A Systematic Review.

COVID-19 is a public health emergency all around the world. Severe illness occurred in about 14% of patients and 5% of patients developed critical illness, but the prognosis for these patients remains unclear. To describe the prognosis in hospitalized adults with COVID-19. The MEDLINE, EMBASE, AMED, and COCHRANE databases were searched for studies published up to 28 June 2021 without language restrictions. Descriptors were related to "COVID-19" and "prognosis". Prospective inception cohort studies that assessed morbidity, mortality and recovery in hospitalized people over 18 years old with COVID-19 were included. Two independent reviewers selected eligible studies and extracted the available data. Acute respiratory distress syndrome (ARDS) and multiple organ failure (MOFS) were considered as outcomes for morbidity and discharge was considered for recovery. The Quality in Prognosis Studies (QUIPS) tool was used to assess risk of bias. Analyses were performed using Comprehensive Meta-Analysis (version 2.2.064). We included 30 inception cohort studies investigating 13,717 people hospitalized with COVID-19 from different countries. The mean (SD) age was 60.90 (21.87) years, and there was high proportion of males (76.19%) and people with comorbidities (e.g., 49.44% with hypertension and 29.75% with diabetes). Findings suggested a high occurrence of morbidity, mainly related to ARDS. Morbidity rates varied across studies from 19% to 36% in hospital wards, and from 13% to 90% in Intensive Care Units-ICU. Mortality rates ranged from 4% to 38% in hospital wards and from 8% to 51% in ICU. Recovery rates ranged up to 94% and 65% in hospital wards and ICU, respectively. The included studies had high risk of bias in the confounding domain. The prognosis of people hospitalized with COVID-19 is an issue for the public health system worldwide, with high morbidity and mortality rates, mainly in ICU and for patients with comorbidities. Its prognosis emphasizes the need for appropriate prevention and management strategies.

Risk of SARS-CoV-2 Reinfections in a Prospective Inception Cohort Study: Impact of COVID-19 Vaccination.

The risk of reinfection could be related to the initial SARS-CoV-2 clinical presentation, but there are no data about the risk change after SARS-CoV-2 vaccination. We evaluated the rate of reinfection in an inception cohort study of 4943 health care workers (HCWs) according to symptoms and serologic results during March–May 2020. Incidence rates (IR) and IR ratios (IRR) before and after SARS-CoV-2 vaccination were determined by adjusting Poisson models. Overall, 1005 HCWs (20.3%) referred COVID-19 suggestive symptoms during the first surge of disease, and 33.5% and 55% presented a positive PCR or serology result, respectively. Meanwhile, 13% of asymptomatic HCWs had specific antibodies. During a follow up of 3422.2 person-years before vaccination, the rate of reinfection among seropositive individuals was 81% lower for those who were symptomatic compared with those who were asymptomatic (IRR of 0.19; 95% CI, 0.05–0.67; p = 0.003). During the 3100 person-years period after vaccination, an overall 74% decrease in the rate of infection was observed (IRR of 0.26; 95% CI, 0.21–0.32; p < 0.001), with a significant 83% and 70% decrease in seropositive and seronegative HCWs, respectively. In conclusion, the risk of SARS-CoV-2 reinfections is closely related to the clinical and serological presentation of COVID-19. COVID-19 vaccination further decreases the risk of reinfection more markedly among seropositive.

Clinical significance of soluble interleukin-2 receptor measurement in patients with idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (iRPF) is a rare chronic fibro-inflammatory disorder of unknown etiology. Activated T-helper cells, which shed soluble interleukin-2 receptor (sIL-2R) into the circulation, may play a pathogenetic role. Hence, measuring sIL-2R may be of value in monitoring disease activity and treatment response in iRPF patients. We performed a prospective inception cohort study of 82 patients with untreated (re)active iRPF stratified by elevated (> 623U/mL) or normal sIL-2R level at baseline and compared disease characteristics among these groups. Baseline and changes in sIL-2R levels following treatment with tamoxifen (TMX) or prednisone (PDN) were analyzed and related to treatment response. Median sIL-2R level was 668 U/mL (IQR 502.8-827.5); 48 patients (59%) had elevated baseline sIL-2R levels. Patients with elevated sIL-2R presented with higher CRP (P = 0.049) and serum creatinine (sCr) levels (P < 0.001) and more often had hydroureteronephrosis (P = 0.01). There was an age and sex adjusted linear association between baseline sIL-2R and both CRP (P = 0.02) and sCr (P < 0.001). Baseline and serial levels of sIL-2R were predictive and concordant, respectively, with clinical response in patients treated with PDN. ROC curve analyses of sIL-2R on a continuous scale and PDN treatment success showed an AUC of 0.84. A serum sIL-2R cut-off value for PDN treatment success of ≤ 703U/mL was found with a sensitivity of 100% and specificity of 72%. Serial measurement of sIL-2R may be of value in monitoring disease activity and PDN treatment response in iRPF patients.

Nrf2 activation in the human brain after stroke due to supratentorial intracerebral haemorrhage: a case–control study

AimsPharmacological activation of the antioxidative transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) improves outcomes in experimental models of intracerebral haemorrhage (ICH). However, the Nrf2 pathway has not been...

DOP10 Intestinal Ultrasound at IBD diagnosis predicts major disease events – A Copenhagen IBD cohort study

Abstract Background The disease course of inflammatory bowel disease (IBD) is heterogeneous and highly unpredictable. Intestinal Ultrasound (IUS) is a non-invasive modality capable of assessing disease activity in IBD. IUS is reliable, patient-friendly, and allows frequent monitoring of disease activity. However, the evidence for IUS as a predictor of disease course is still limited. Here we present novel data on the predictive value of IUS performed at the time of IBD diagnosis. Methods Patients with new-onset IBD are currently being included in the ongoing multicentre prospective inception cohort study, the IBD Prognosis Study. During the first five years following diagnosis, patients undergo regular clinical, biochemical, endoscopic, and imaging assessments. IBD treatment and disease events are prospectively recorded. IUS is performed at diagnosis, after three months, and hereafter annually. Patients with proctitis do not undergo assessment with IUS. The newly developed IUS score, the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), is calculated for the most inflamed segment, with a high score indicating severe disease activity. The score incorporates bowel wall thickness (BWT), bowel wall stratification, colour Doppler signal, and inflammatory fat. In this abstract, we report our preliminary results after including patients for six months. Results IBUS-SAS at diagnosis was available in 60 patients. 32 patients were diagnosed with Crohn’s disease (ilieal: 7, colonic: 19, ileocolonic: 6) and 28 patients were diagnosed with ulcerative colitis (UC) or unclassified IBD (proctitis: 1, left-sided colitis: 8, extensive colitis: 19). The mean IBUS-SAS at diagnosis was 51.1, with a mean BWT of 5.2 mm. Major clinical outcomes were initiation of biologic therapy, n=12 (20.0%), IBD-related bowel resection, n=5 (8.3%), IBD-related hospitalisation, n=19 (31.7%). The mean IBUS-SAS at diagnosis was 66.2 among patients with the combined endpoint of any of these disease outcomes during follow-up vs. 34.7 for no major outcomes (p&amp;lt;0.001), see Figure 1. Additionally, we found that all patients with an IBUS-SAS above 80 at diagnosis had been hospitalised and started on systemic steroids. So far, 20 patients had an IUS follow-up scan after three months showing a mean IBUS-SAS reduction by 17.0 points (p=0.008). Conclusion We present data on the predictive value of early IUS in new-onset IBD. IUS activity at diagnosis of IBD seems to have the capability to predict short term disease outcome. At diagnosis, high IBUS-SAS is associated with major disease events such as starting biological therapy, IBD-related bowel resection, and IBD-related hospitalisation. Furthermore, response to treatment is reflected by a decrease in IBUS-SAS after three months.

Prevalence of Long COVID symptoms in Bangladesh: a prospective Inception Cohort Study of COVID-19 survivors

BackgroundThe objective of this study was to identify the prevalence of long COVID symptoms in a large cohort of people living with and affected by long COVID and identify any...

SP6.1.9 Colorectal Cancer and Synchronous Liver-limited Metastatic Disease: The final results of the CoSMIC Inception Cohort Study

Abstract Aims Currently, evidence is inadequate to inform the selection of optimal treatment for patients with colorectal cancer and synchronous liver-limited hepatic metastases. Options include synchronous or staged surgery integrated with systemic chemotherapy. CoSMIC is the first inception cohort study to follow patients from point of presentation in order to identify factors influencing treatment and outcome. Methods Patients were identified at presentation to the regional liver metastases MDT at Manchester Royal Infirmary between April 2015-2018. Data were collected on demographics, intervention and outcome. The study was approved by Regional Ethics Committee (REC reference: 14/NW/1397). Results Of 125 patients recruited, 109 underwent surgery with 18 (17%) liver-first, 75 (69%) bowel-first and 16 (14%) undergoing synchronous resection. There were no differences in baseline demographics or co-morbidity. Eighty-eight completed the intended surgical pathway, with highest failure in liver-first patients where 39% did not proceed to subsequent bowel resection. Critical care occupancy between staged and synchronous resections (5.6 versus 5.2 days; P = 0.92), and inpatient stay (16.5 versus 16.8 days; P = 0.92) was not significant. There was no 30-day mortality. Cox regression analysis identified surgical sequence as a significant covariate (Х2= 31.3; P &amp;lt; 0.001). Survival was similar between surgical groups (Log-rank test; P = 0.87). Conclusions CoSMIC is the first prospective inception cohort study of colorectal cancer and synchronous liver-limited metastasis. The study population is small and from a single centre and thus could be influenced by recruitment and sample bias. However, the important novel finding is that there is no survival difference between treatment pathways.

Prevalence of Long COVID Symptoms in Bangladesh: A Prospective Inception Cohort Study of COVID-19 Survivors

Background: The aim of this study was to identify the prevalence of ‘Long COVID’ symptoms (LCS) in a large cohort of survivors and identify any potential associated risk factors.Methods: A prospective survey was undertaken of an inception cohort of confirmed COV|ID-19 survivors (Aged 18 to 87 years). 14392 participants were recruited from 24 testing facilities across Bangladesh between June, and November 2020. All participants had a previously confirmed positive COVID-19 diagnosis, and reported persistent symptoms and difficulties in performing daily activities. Participants who consented, were contacted by telephone, and were interviewed regarding LCS, and restriction of activities of daily living. Cardio-respiratory parameters were also measured. Statistical analysis included binary logistic and multiple linear regressions were performed with LCS as the dependent variable. Associated risk factors were identified using Structural Equation Modelling (SEM).Findings: Among 2198 participants, the prevalence of LCS at 12 weeks was 16·1%. Overall, eight LCS were identified and in descending order of prominence are: fatigue, pain, dyspnea, cough, anosmia, appetite loss, headache, and chest pain. COVID survivors experienced between 1 to 5 LCS with an overall duration period of 21·8 ± 5·2 weeks. SEM predicted the length of LCS to be related to younger age, female gender, rural residence, prior functional limitation and smoking.Interpretation: In this cohort of survivors, at 31 weeks post diagnosis, the prevalence of LCS was 16·1%. The risk factors identified for presence and longer length of LCS warrant further research and consideration to support public health initiatives.Clinical Trial Registration Details: The study was registered at World Health Organization (WHO) Primary Clinical trial registry platform (CTRI/2020/09/028165) on 30/09/2020 with the title “Symptoms presentation among the COVID-19 survivors in Bangladesh”.Funding Information: No funding.Declaration of Interests: We declare no competing interests.Ethics Approval Statement: Ethical permission was obtained from the Institutional Review Board at the Institute of Physiotherapy, Rehabilitation, and Research (Ethical review committee at Bangladesh Physiotherapy Association) on September 17, 2020 (BPA-IPRR/IRB/17/09/2020/028). Verbal consent was obtained during the initial telephone call and written consent was obtained at interview. The principles of the Helsinki Declaration19 were followed throughout the research to ensure confidentiality, ethics and privacy.

Osteoporotic Fractures and Vertebral Body Reshaping in Children With Glucocorticoid-treated Rheumatic Disorders.

Osteoporotic fractures are an important cause of morbidity in children with glucocorticoid-treated rheumatic disorders. This work aims to evaluate the incidence and predictors of osteoporotic fractures and potential for recovery over six years following glucocorticoid (GC) initiation in children with rheumatic disorders. Children with GC-treated rheumatic disorders were evaluated through a prospective inception cohort study led by the Canadian STeroid-induced Osteoporosis in the Pediatric Population (STOPP) Consortium. Clinical outcomes included lumbar spine bone mineral density (LS BMD), vertebral fractures (VF), non-VF, and vertebral body reshaping. A total of 136 children with GC-treated rheumatic disorders were enrolled (mean age 9.9 years, SD 4.4). The 6-year cumulative fracture incidence was 16.3% for VF, and 10.1% for non-VF. GC exposure was highest in the first 6 months, and 24 of 38 VF (63%) occurred in the first 2 years. Following VF, 16 of 19 children (84%) had complete vertebral body reshaping. Increases in disease activity and body mass index z scores in the first year and declines in LS BMD z scores in the first 6 months predicted incident VF over the 6 years, while higher average daily GC doses predicted both incident VF and non-VF. LS BMD z scores were lowest at 6 months (mean -0.9, SD 1.2) and remained low by 6 years even when adjusted for height z scores (-0.6, SD 0.9). VF occurred early and were more common than non-VF in children with GC-treated rheumatic disorders. Eighty-four percent of children with VF underwent complete vertebral body reshaping, whereas vertebral deformity persisted in the remainder of children. On average, LS BMD z scores remained low at 6 years, consistent with incomplete recovery.

Socio-economic position as a moderator of cardiometabolic outcomes in patients receiving psychotropic treatment associated with weight gain: results from a prospective 12-month inception cohort study and a large population-based cohort

Weight gain and metabolic complications are major adverse effects of many psychotropic drugs. We aimed to understand how socio-economic status (SES), defined as the Swiss socio-economic position (SSEP), is associated with cardiometabolic parameters after initiation of psychotropic medications known to induce weight gain. Cardiometabolic parameters were collected in two Swiss cohorts following the prescription of psychotropic medications. The SSEP integrated neighborhood-based income, education, occupation, and housing condition. The results were then validated in an independent replication sample (UKBiobank), using educational attainment (EA) as a proxy for SES. Adult patients with a low SSEP had a higher risk of developing metabolic syndrome over one year versus patients with a high SSEP (Hazard ratio (95% CI) = 3.1 (1.5–6.5), n = 366). During the first 6 months of follow-up, a significant negative association between SSEP and body mass index (BMI), weight change, and waist circumference change was observed (25 ≤ age < 65, n = 526), which was particularly important in adults receiving medications with the highest risk of weight gain, with a BMI difference of 0.86 kg/m2 between patients with low versus high SSEP (95% CI: 0.03–1.70, n = 99). Eventually, a causal effect of EA on BMI was revealed using Mendelian randomization in the UKBiobank, which was notably strong in high-risk medication users (beta: −0.47 SD EA per 1 SD BMI; 95% CI: −0.46 to −0.27, n = 11,314). An additional aspect of personalized medicine was highlighted, suggesting the patients’ SES represents a significant risk factor. Particular attention should be paid to patients with low SES when initiating high cardiometabolic risk psychotropic medications.

Inhibitor Screening in Severe Hemophilia a: A Six-Year Single Center Experience

Background : Factor VIII (FVIII) inhibitors comprise the most morbid and expensive complication in severe hemophilia A. Inhibitor risk is known to be highest within the first 50 exposures to FVIII replacement products, with greatest risk during the first 20 exposures. Routine inhibitor screening is typically performed frequently with the first 20 to 50 exposures, but screening after 50 exposures is controversial, given the high cost of testing and unknown benefit. Early inhibitor detection allows effective treatment of bleeding with bypassing agents, and prompt initiation of immune tolerance to eradicate the inhibitor. Here we report inhibitor screening results at the University of Colorado Hemophilia and Thrombosis Center. Methods : This is a retrospective review of inhibitor testing data from study participants with severe hemophilia A enrolled, with Institutional Review Board approved informed consent, in the Hemophilia Prospective Inceptional Cohort Study (HEMO-PICS) from April 1, 2011 through April 1, 2017. A positive inhibitor was defined as modified Nijmegen Bethesda titer ≥0.5 confirmed on 2 separate blood draws. Tolerance was defined as a Bethesda titer <0.5 on two or more samples. The clinical protocol prescribed inhibitor screening in severe hemophilia A patients every 3-5 exposures prior to 50, and annually thereafter in accordance with National Hemophilia Foundation and US Centers for Disease Control recommendations. Results : Of 204 participants with severe hemophilia A in the study cohort, 24 had fewer than 50 factor exposures and were inhibitor negative at the start of the study observation period (“<50 Exposures Group”), 13 participants had a positive inhibitor at the start of the observation period (“+ Inhibitor Group”), and 167 had >50 exposures and a history of either no inhibitor or a tolerized inhibitor (“>50 Exposures Group”). Figure 1 shows inhibitor surveillance rates and results. In participants with < 50 exposures, positive inhibitors were detected in 11/42 screening tests, while participants with > 50 exposures had 0 positive inhibitors in 454 screening tests. In the “<50 Exposures Group”, 11 of 24 (45%) developed an inhibitor, 7 high titer (peak range 16.7 - 185 BU/mL) and 4 low titer (peak range 0.7 - 1.8 BU/mL). Six participants achieved 50 exposures without inhibitor development during the observation period, while the remaining 7 had fewer than 50 factor exposures at the end of the study period. The mean (+/- standard deviation) age of inhibitor development was 14.6 (+/- 6.2 [range 3-22]) months, after a mean of 12.8 (+/- 7.9 [range 1-29]) factor exposures. Six of those who developed inhibitors did so prior to starting prophylaxis, and the other 5 patients developed inhibitors within 2 months of prophylaxis initiation. Of those who did not develop inhibitors, 8 have been on prophylaxis for an average of 36 (+/- 23.8 [range 14-80]) months, 3 are planning to start prophylaxis, and 2 have declined. Of the 13 participants in the “+ Inhibitor Group”, 3 were tolerized during the study. Conclusion : We report a high rate of positive inhibitor surveillance tests in severe hemophilia A patients during the first 50 exposures (1 per 3.8 tests), and very low rates of positive inhibitors in this population following 50 exposures (0/454). While our results reinforce the practice of frequent inhibitor screening in patients with < 50 factor exposures, screening for inhibitors in patients with > 50 exposure days and no change in the bleeding phenotype is unlikely to be clinically relevant and should not be routinely performed. [Display omitted] DisclosuresWarren:CSL Behring Heimburger Award: Research Funding; Bayer Hemophilia Awards Program: Research Funding. Ng:CSL Behring Heimburger Award: Research Funding; Shire: Consultancy. Buckner:Shire: Membership on an entity's Board of Directors or advisory committees; Uniqure: Consultancy; Genentech: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees.